Eli Lilly’s Pirtobrutinib Joins the Race as BTK Competition Heats Up

On December 16, Innovent Biologics and Eli Lilly announced a collaboration agreement for the non-covalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor, pirtobrutinib, in mainland China. Under this agreement, Innovent Biologics will handle the import, sales, promotion, and distribution, while Eli Lilly will manage R&D and post-market medical affairs.

On October 29, Eli Lilly’s pirtobrutinib received approval from the National Medical Products Administration (NMPA) for treating relapsed or refractory mantle cell lymphoma (MCL) in adults who have previously received BTK inhibitor treatments. Currently, the domestic market has five approved BTK inhibitors, including ibrutinib, zanubrutinib, ocatabrutinib, and acabrutinib.

Sanofi’s Tolebrutinib and Rilzabrutinib are in Phase III clinical trials, while CT-1530 from Shouyao Holdings is in Phase II. The robust development of BTK inhibitors indicates potential market changes.

BTK inhibitors work by targeting the BCR signaling pathway, binding to BTK, inhibiting its phosphorylation, and inducing apoptosis, effectively managing B-cell malignancies. Before BTK inhibitors, lymphoma treatments were limited to chemotherapy, anti-CD20 antibodies, and radiotherapy.

Ibrutinib, the first BTK inhibitor, revolutionized B-cell cancer treatment since its 2013 debut and was approved in China in 2017. However, sales of ibrutinib have slowed due to competition from similar drugs. Zanubrutinib, developed by BeiGene, reached $1.297 billion in global sales in 2023, marking the first domestic drug to achieve such success, but it now faces increasing competition.

Pirtobrutinib, as the first and only non-covalent BTK inhibitor, intensifies competition in this niche market. It shows potential to overcome resistance to covalent BTK inhibitors and offers a new option for relapsed/refractory MCL patients.

To highlight its efficacy, Eli Lilly conducted a head-to-head study in the BRUIN MCL-321 trial. By 2030, pirtobrutinib is projected to capture 60% of the chronic lymphocytic leukemia market, equating to $3 billion in annual sales.

With advancing technology and new drug development, the BTK market is expanding rapidly. According to Frost & Sullivan, the global BTK market could reach $20 billion by 2025 and $26.1 billion by 2030. In China, the market size is expected to reach RMB 13.1 billion by 2025 and RMB 22.5 billion by 2030.

The growing BTK market has attracted numerous pharmaceutical companies. At least 20 BTK inhibitors are in clinical trials domestically, with Shouyao Holdings, Hengrui Medicine, and Hezheng Pharmaceutical leading the way. Ibrutinib’s core patent will expire on December 28, 2026, and at least 10 companies are preparing generics. This will lead to fierce competition among original drugs, domestic innovations, and generics.

BeiGene’s zanubrutinib remains a key product, but new competitors like pirtobrutinib pose challenges. The success of pirtobrutinib in China’s market is worth monitoring.

Originally developed by Redx Pharma and acquired by Loxo Oncology, pirtobrutinib was purchased by Eli Lilly for $8 billion in 2019. In March 2022, Innovent Biologics secured Chinese commercialization rights for pirtobrutinib with an initial payment of $45 million.

The partnership between Innovent Biologics and Eli Lilly began in 2015 and has expanded through multiple projects. Despite setbacks like sintilimab’s rejection by the U.S. FDA in 2022, their collaboration continues with other initiatives.

Their 2019 cooperation on IBI362, a dual GLP-1R and GCGR agonist, is in Phase II/III trials for Type 2 diabetes and weight loss.

In March 2022, Eli Lilly’s ramucirumab was approved in China, granting Innovent Biologics exclusive commercialization rights. Additionally, they collaborate on selpercatinib, a RET inhibitor for gene fusion tumors.

The cooperation and competition between domestic and multinational pharmaceutical companies are becoming a norm. This model offers a win-win strategy for navigating the global market.